Broadly, this proposal examines the pathogenesis, and primarily the immunogenetic aspects, of Juvenile Rheumatoid Arthritis (JRA), the major crippling arthropathy of childhood. An immunogenetic (HLA) influence in this disease has been established; however, the critical predisposing genes and their products are unknown. Present knowledge of autoimmune diseases like JRA suggests that products of HLA genes and T-lymphocyte receptor genes interact with a putative disease-associated antigen to form a trimolecular complex that results in disease expression. The research proposed here is designed to identify the HLA genes and their products (epitopes) critical to formation of this complex in children with early onset pauciarticular types of JRA. HLA associations with this form of JRA are unique among childhood arthropathies. Specifically, HLA genes will be sequenced utilizing the polymerase chain reaction, to facilitate the process. The long-term goals of the project are the development of probes and antibodies that are epitope specific and can be used for future investigational, diagnostic, and perhaps therapeutic purposes.